Enforcing surveillance of antimicrobial resistance and antibiotic use to drive stewardship: experience in a paediatric setting.

BACKGROUND: Antibiotic stewardship (AS) interventions in paediatrics are still not standardized regarding methodology, metrics, and outcomes. We report the results of an AS intervention in the paediatric area based on education and guideline provision via an electronic App. MATERIALS AND METHODS: The AS intervention was conducted in 2021 through observation, education, audit and feedback and provision of an electronic App (Firstline.org) to support antibiotic prescription based on local susceptibility data. The primary outcome was the antibiotic consumption in the 12 months following the intervention (year 2022) compared with a historical 12-month control (year 2019) via an interrupted time series analysis. Secondary outcomes were appropriateness of therapy, length of stay, 30-day readmission, transfers to the paediatric intensive care unit, in-hospital mortality, and prevalence of antimicrobial resistance (AMR). RESULTS: During the post-intervention phase, 29 cross-sectional audits and feedback were conducted including 467 patients. Prescriptions were appropriate according to the guidelines in 85.7% of cases, with a stable trend over time. A significant decrease in antibiotic consumption was measured in terms of defined daily doses per 1000 patient days (-222.13; P<0.001) and days of therapy per 1000 patient days (-452.49; P<0.001) in the post-intervention period with a clear inversion of the Access to Watch ratio (from 0.7 to 1.7). Length of stay, in-hospital mortality, intensive care unit transfers, and incidence of AMR infections remained stable, while 30-day readmission decreased from 4.9 per 100 admissions to 2.8 per 100 admissions (P<0.001). CONCLUSIONS: The intervention was associated with a significant reduction in antimicrobial consumption and an increase in the appropriateness of prescriptions. Electronic tools can be of value in promoting adherence to guidelines and ensuring the sustainability of results.

Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience.

INTRODUCTION: Mitochondrial fatty acid oxidation disorders (FAODs) are a heterogeneous group of hereditary autosomal recessive diseases included in newborn screening (NBS) program in Italy. The aim of this study was to analyse FAODs cases, identified either clinically or by NBS,for clinical and genetic characterization and to evaluate a five years' experience of NBS, in the attempt to figure out the complexity of genotype-phenotype correlation and to confirm the clinical impact of NBS in our centre experience. MATERIALS AND METHODS: We analysed FAODs patients diagnosed either by NBS or clinically, followed since February 2014 to April 2019 at the Regional Screening Centre and Inherited Metabolic Diseases Unit of Verona. Diagnosis was confirmed by plasma acylcarnitines, urinary organic acids, enzymatic and genetic testing. For not clear genotypes due to the presence of variants of uncertain significance, in silico predictive tools have been used as well as enzymatic activity assays. Patients underwent clinical, nutritional and biochemical follow up. RESULTS: We diagnosed 30 patients with FAODs. 20 by NBS: 3 CUD, 6 SCADD, 5 MCADD, 4 VLCADD, 2 MADD. Overall incidence of FAODs diagnosed by NBS was 1:4316 newborns. No one reported complications during the follow up period. 10 patients were diagnosed clinically: 2 CUD, 2 CPT2D, 1 VLCADD, 5 MADD. Mean age at diagnosis was 29.3 years. Within this group, complications or symptoms were reported at diagnosis, but not during follow-up. 12 mutations not previously reported in literature were found, all predicted as pathogenic or likely pathogenic. DISCUSSION AND CONCLUSIONS: Our study highlighted the great phenotypic variability and molecular heterogeneity of FAODs and confirmed the importance of a tailored follow up and treatment. Despite the short duration of follow up, early identification by NBS prevented diseases related complications and resulted in normal growth and psycho-motor development as well.

Childhood Asthma Control Test and airway inflammation evaluation in asthmatic children.

BACKGROUND: The Childhood Asthma Control Test (C-ACT) has been proposed as a tool in assessing the level of disease control in asthmatic children. To evaluate the position of C-ACT in the clinical management of asthmatic children, in relationship to the level of airway inflammation as assessed by fractional exhaled nitric oxide (FeNO) and with lung function. METHODS: A total of 200 asthmatic children were included in the study: 47 children with newly diagnosed asthma ('New') and without any regular controller therapy; and 153 children with previously diagnosed asthma, treated according to GINA guidelines, and evaluated during a scheduled follow-up visit ('Follow-up'). Childhood Asthma Control Test, FeNO and lung function [forced expiratory volume 1 (FEV1) and forced vital capacity (FVC)] were evaluated. RESULTS: In New vs Follow-up participants, C-ACT score (P < 0.001), FVC (P < 0.005) and FEV1 (P < 0.05) were significantly lower, and FeNO (P = 0.011) were significantly higher. In New, but not in Follow-up participants, significant correlations were observed between C-ACT score and FeNO (r = -0.51; P < 0.001), FEV1 (r = 0.34; P = 0.022) and FEV1/FVC (r = 0.32; P = 0.03). This lack of correlation in Follow-up visits seemed attributable to dissociation between inadequately controlled asthma by C-ACT ratings with normalization of other measures such as FeNO levels. CONCLUSIONS: This study confirms and expands the concept that C-ACT is complementary to, but not a substitute for, other markers of disease control in asthmatic children, especially in the context of follow-up visits.

Prevalence and risk factors for atopic dermatitis in preschool children.

BACKGROUND: Atopic dermatitis (AD) is a common condition in infancy which usually disappears by 3 years of age in a significant proportion of children. The prognosis is mostly determined by severity and presence of atopic sensitization. OBJECTIVES: To investigate prevalence of AD, comorbidities and risk factors in a population of preschool children aged 3-5 years. METHODS: Children in kindergartens were evaluated. The International Study of Asthma and Allergies in Childhood written questionnaire (WQ) was used, with additional questions on risk factors. Atopy was investigated by skin prick tests. RESULTS: One thousand, four hundred and two valid WQs (92% response rate) were returned for evaluation. The prevalence of AD symptoms in the last 12 months in the whole population was 18.1% (254 cases). Seventy-two per cent of these children presented AD-specific localizations. The prevalence of eczema as a doctor's diagnosis in the total population was 15.4%. Positive atopic sensitization was present in 18.6% of the total and in 32.2% of the AD study population, respectively. Multiple sensitivities were observed in 58.2% of sensitized children. The prevalence of sensitization demonstrated that the most common sensitizing allergens in children with AD were mites and grass pollen. Rhinitis symptoms and wheezing were present in 32.2% and 24.2%, respectively, of children with AD. Allergic sensitization to egg, cat, grass pollen and mites, as well as the presence of symptoms of rhinitis, and a positive family history of atopy were all significant risk factors for AD. CONCLUSIONS: The study demonstrates a high prevalence of AD and a close relationship with rhinitis symptoms. Significant risk factors for AD were sensitization to food or inhalant allergens as well as parental history of atopy.

Transforming growth factor-beta and interleukin-10 in breast milk and development of atopic diseases in infants.

BACKGROUND: Precise relationship between breastfeeding and infant allergy is poorly understood. Objective Aim was to quantify TGF-beta(1) and IL-10 in colostrum and mature milk from allergic and non-allergic mothers and to verify relationship with allergic disease development. METHODS: Mothers (13 allergics, nine controls) of 22 newborns participated to prospective study on development of children atopy. Colostrum and mature milk were assayed for TGF-beta(1) and IL-10 by ELISA. Children underwent paediatrician evaluation at 6 months of life. RESULTS: Data are presented as median values and range. A significant difference in concentration of TGF-beta(1) between colostrum (330, range 0-3400 pg/mL) and mature milk (215, range 0-2400 pg/mL) was observed in samples from allergic mothers (P=0.015). In mature milk TGF-beta(1) was significantly lower in allergic (215, range 0-2400 pg/mL) than in non-allergic mothers (1059, range 0-6250 pg/mL) (P=0.015). IL-10 was weakly expressed without significant differences between allergic (4.8, range 0-42 and 9.5, range 0-42 pg/mL in colostrum and in mature milk) and non-allergic mothers (0, range 0-42 pg/mL in colostrum and 0, range 0-42 pg/mL in mature milk). After 6 months 46% infants from allergic mothers, but none from controls, presented atopic dermatitis. CONCLUSION: TGF-beta(1) was significantly less secreted in mature milk of allergic mothers, while no difference in IL-10 was found. Particular cytokine patterns in milk could influence development of atopic diseases. Further immunological studies in this field are necessary.

[Treatment of tumors by local hyperthermia in urology and gynecology (author's transl)]. / Hyperthermie localisée dans le traitement des tumeurs en urologie et en gynécologie. Phase expérimentale chez l'animal et phase clinique chez l'homme.

An experimental study by the authors, on the effects of local-regional hyperthermia on bladder B.N.A. induced carcinoma of the dog has been going on since 1966. The authors have observed complete disappearance in the animals of the mucosa and sub-mucosa neoplasia, even after 6 years from the date of treatment. The sterilization of the neoplastic surface was checked by several histological sections observations on two excised bladders. As the results showed no negative secondary effects, the authors have started, since 1973, a clinical study of hyperthermia treatment of the bladder, vagina, female urethra and rectum stump carcinoma. Heat was obtained and introduced into the bladder by leans of an apparatus specifically designed for this purpose; the double-circuit terminal probe supplies a thermocouple controlled constant temperature. We are submitting the cases treated together with a discussion on results obtained and problems faced.

[Results of hyperthermia on the bladder carcinomas of the dog (author's transl)]. / Résultats de l'hyperthermie locale sur les carcinomes de la vessie du chien

A study on the effects of hyperthermia on B.N.A. induced bladder carcinomas of the dog has been carried out since 1966. The hyperthermic treatment has been performed directly in the bladder using an original equipment especially designed. In a large majority of the animals definite cancericidal changes have been shown. The most favorable results were obtained in the treatment of carcinomas not infiltrating the muscular layer of the bladder. In these cases malignant recurrency was not shown up to five years after treatment. Good palliative effect is also refferred in the treatment of advanced bladder carcinoma of the man.